•LUNG PATHOLOGY

Dr. Sofia Zilber

PNEUMONIA – any infection of the lung parenchyma.

(although this term is used for many interstitial non infectious lung diseases).

Defense mechanisms

•Upper airways – nasal clearance

•Trachea, bronchi –mucociliary clearing

•Lungs - alveolar macrophages

•Immune system: immunoglobulins, cell-

mediated immunity

�One type of pneumonia predisposes to another (the most common cause of death

in viral influenza epidemics is bacterial pneumonia)

�The portal of entry for most pneumonias is the respiratory tract. Hematogenousspread from other organs can occur.

�Many patients with chronic diseases acquire terminal pneumonia while

hospitalized (nosocomial infection).

Classification of pneumonia

•By specific etiologic agent•By the clinical setting in which the infection

occurs

Morphology of bacterial pneumonia

•Lobar pneumonia

•Lobular pneumonia (bronchopneumonia)

The patterns overlap!

Lobar pneumonia

•Fibrino-suppurativeconsolidation of a large portion of a lobe or an entire

lobe

Lobar pneumonia stages

•Congestion•Red hepatization•Gray hepatization•Resolution

•Congestion- vascular engorgement, few neutrophils and bacteria in alveoli.

•Red hepatization – massive exudation with red cells, neutrophils and fibrin.

•Gray hepatization – disintegration of RBC, fibrinosuppurative exudate.

•Resolution – progressive enzymatic digestion of exudate.

Red hepatization

Organizing pneumonia

Early organization

Bronchopneumonia•Patchy consolidation of

the lungs ( areas of acute suppurative

inflammation)•May be patchy through

one lobe but more often multilobar ,

bilateral and basal.•Micro: Suppurative

inflammation in bronchi, bronchioles

and alveoli.

BronchopneumoniaBronchopneumonia

Patchy area of alveoli are filled with inflammatory cells. The alveolar structure is still maintained, which is why a pneumonia often resolves with minimal residual destruction or damage to the lung.

Bronchopneumonia

Complications of pneumonia

•Abscess formation ( Klebsiella, pneumococci)

•Empyema•Organization of the exudate•Bacteremic dissemination

Pleuritis

The pleural surface demonstrates areas of yellow-tan purulent exudate.(Pleuritis).

��Organization of the Organization of the exudateexudate

Morphology of atypical pneumonia

•Interstitial inflammatory infiltrate composed of mononuclear cells and sometimes

neutrophils.•Intraalveolar proteinaceous material and

hyaline membranes, reflecting alveolar wall damage (DAD).

•Viral pneumonias - necrosis of bronchial and alveolar epithelium and cytopathic

changes

Viral pneumonia with interstitial lymphocytic infiltrates. Note that there is no alveolar exudate.

Atypical pneumoniaAtypical pneumonia

Interstitial pneumonia

Nosocomial (hospital-acquired) pneumonia

•Gram- negative rods (Klebsiella, Enterobacter, Pseudomonas)

•Staphylococcus aureus (usually penicillin-resistant)

•Common in patients with severe underlying disease.

Aspiration pneumonia

•Occurs in markedly debilitated patients.•Partly chemical, partly bacterial, from the

oral flora: anaerobic –Bacteroides, Fusobacterium,

Peptostreptococcus; aerobic– Streptococcus pneumonia,

Staphylococcus aureus Haemophilisinfluenzae and Pseudomonas aeruginosa.

Aspiration pneumonia

•Necrotizing pneumonia

•Fulminate clinical course

•Common complication-

lung abscess

formation

Lung Abscess

•Local suppurative process with necrosis of lung tissue.

•Causative organisms: aerobic and anaerobic

streptococci, Staphylococcus aureus,

gram-negative organisms and anaerobes from the oral cavity.

Lung Abscess mechanisms of development

•Aspiration of infective materials and gastric contents.

•Antecedent primary bacterial infections.•Septic embolism.•Neoplasia (secondary obstruction)•Lung trauma and spread of infections from

a neighboring organs.•Primary cryptogenic lung abscess

Lung abscess

Lung abscess morphology

•Aspiration abscess- Rtside and single

•Abscess due to pneumonia and

bronchiectases multiple, basal.

•Septic – haphazard, multiple.

•Suppurative destruction of lung within the central

area of cavitation!

Chronic Pneumonia•A localized lesion in immunocompetent

patient.•Causative agents:

NocardiaActinomyces

Histoplasma capsulatumCoccidoides immitis

Blastomyces dermatitidisMycobacterium (discussed separately)

•Morphology – granulomatous inflammation

Pneumonia in the immunocompromised host

•CMV•Pneumocystis carinii•Mycobacterium avium intracellulare•Invasive aspergillosis•Invasive candidiasis•“Usual” bacterial, viral and fungal

organisms

Pneumocystis carinii

•Occurs predominantly in immunosuppressed persons.

•Pneumocystis is a FUNGUS!•Clinically – fever, dyspnea and dry cough

progressing to respiratory failure.•Radiologically – bilateral alveolar and

interstitial infiltrates radiating from the hilus.•Diagnosis – BAL and lung biopsy

PCP morphology

•Foamy intraalveolar exudate•Interstitial pneumonia•Diffuse Alveolar Damage (DAD)

•GMS (Gomory methenamine silver) stain highlights cysts containing sporosoites and

free throphozoites. Cysts – 4-6µm in diameter with one or two

dots.•Monoclonal antibodies to pneumocystis.•In situ hybridization and PCR

Identification of organisms

CMV (β-group herpesvirus)

•CMV infects and remains latent in WBC and can be reactivated when immune

status is depressed.•The major envelop glycoprotein of CMV

binds to EGFR.•CMV pneumonia clinical features: fever,

dyspnea, nonproductive cough, diffuse chest infiltrates.

CMV morphology

•Focal or diffuse interstitial pneumonia•Enlargement of infected cells; epithelial

and endothelial cells are involved. •Intranuclear inclusions surrounded by

clear halo. In some cells - cytoplasmicinclusions (basophilic granules).

•Virus identification: immunohistochemistry, PCR.

CMV pneumonia

AspergillosisSecond most common fungal pathogen after Candida. Septate hypae branched at 45 ˚angle

Patterns of pulmonary aspergillosis:ColonisationFungus ball

Hypersensitivity reactionAllergic bronchopulmonary aspergillosis

Eosinophilic pneumoniaHypersensitivity pneumonitis

Invasive (in immunosuppressed)Acute invasive aspergillosis

Chronic necrotizing pneumonia

(usually angiocentric, produce infarcts)

Mycobacteria

•Slender aerobic rods growing in strait or branching chains.

•Mycobacterium have a waxy cell wall composed of mycolic acid which makes

them acid fast - they retain stains on treatment with a mixture acid and alcohol -

Ziehl –Neelsen stain.

a ZiehlFranz (described by two German doctors; a pathologist)NeelsenFriedrich bacteriologist and

Tuberculosis epidemiology

•Leading infectious case of death in the world after HIV.

•HIV makes people susceptible to TB•Other conditions, like diabetes, renal

failure, chronic lung disease, alcoholism and others increase risk of TB.

•The disease affects people from low socio-economic levels

Clinical features of TB

•Primary TB develops in a unsensitizedperson. Latent disease. Rare –

progressive infection.•Secondary TB arises in a previously

sensitized person. May occur: 1) shortly after primary

2) from reactivation of dormant primary lesions (most common)

3) reinfection

Primary pulmonary TB

•Subpleural 1-1.5cm area of granulomatous

inflammation (Ghonfocus) + hilar lymph

nodes involvement = Ghon complex.

•Subsequent fibrosis and calcifications of Ghon

complex.

Secondary tuberculosis

•The initial lesion - focus of consolidation with variable amount of central caseationor peripheral fibrosis in apical subpleural

location.•Progressive pulmonary TB – enlarged

lesion with expanded caseation. •Miliary TB – up to 2 mm lesions that may

coalesce.•Pleural involvement: effusion, TB

empyema, obliterative fibrous pleuritis.

Secondary tuberculosis•Endobronchial, endotracheal, laryngeal

TB.•Systemic miliary TB •Isolated-organ TB (meningies, kidneys,

adrenals, bones, fallopian tubes etc. Vertebral TB- Pott’s dis. Paraspinal “cold

abscesses”)•Lymphadenitis ( “scrofula”)•Intestinal TB

Morphology of secondary TB

Cavitation in upper lobes Miliary TB of the spleen

Lung tuberculosis

Histology

Non-Necrotizing granuloma

Necrotizing granuloma Necrotizing granuloma

Mycobacteria on ZN stain

OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASES

Obstructive diseases

Characterized by an increase in resistance to airflow due to partial or complete obstruction at any level, from the trachea to the terminal and respiratory bronchioles

Characterized by an increase in resistance to airflow due to partial or

complete obstruction at any level, from the trachea to the terminal and

respiratory bronchioles

CHRONIC OBSTUCTIVE PULMONARY DISEASE

� EMPHYSEMA

� CHRONIC BRONCHITIS

� BRONCHIAL ASTHMA

� BRONCHIECTASES

EMPHYSEMA

CENTRIACINAR CENTRIACINAR

(CENTRILOBULAR) EMPHYSEMA (CENTRILOBULAR) EMPHYSEMA

Centriacinar emphysema

•Occurs predominantly in heavy smokers•Central portion of the acini is affected•The lesion more severe in the upper

lobes•Black pigment is present in the walls of

the emphysematous space•Inflammation around bronchi and

bronchioles is common

Emphysema centriacinar, severe

PANACINAR (PANLOBULAR) PANACINAR (PANLOBULAR)

EMPHYSEMAEMPHYSEMA

Panacinar emphysema

•Occurs more commonly in the lower zones and in the anterior margins of the lungs

•The acini are uniformly enlarged

•Associated with α1-antitrypsin deficiency

α1-Antitrypsin Deficiency

•Abnormally low serum level of protease inhibitor (Pi)

•Genetics: gene for α1-antitrypsin (chromosome 14) is very polymorphic and

at least 75 forms of protein have been identified.

PiMM is the most common form. PiZZ – only 10% of circulating protein.

Risk of clinical disease.

A.Centrilobular emphysema B. Panlobular emphysema

DISTAL ACINAR (PARASEPTAL) DISTAL ACINAR (PARASEPTAL)

EMPHYSEMAEMPHYSEMA

Paraseptal emphysema

•Upper parts of the lungs are more severely affected

•Involves the lung tissue adjacent to the pleura, along the lobular connective

tissue and at the margins of the lobules•Occurs adjacent to areas of fibrosis,

scarring, atelectasis•Spontaneous pneumothorax in young

adults

Other types of emphysema

Bullous emphysema

•Any form of emphysema that produces large subpleural spaces more than 1 cm in

diameter•Most often subpleural and occurs near the

apex•Rupture of bullae leads to pneumothorax

CHRONIC BRONCHITIS CHRONIC BRONCHITIS

+ +

BRONCHIOLITISBRONCHIOLITIS

Chronic bronchitis

•Persistent cough and sputum production for at least 3 months in at

least 2 consecutive years–Simple chronic bronchtis–Chronic asthmatic bronchitis (+airways

hyperreactivity)

–Chronic obstructive bronchitis (+airflow obstruction and emphysema)

CHRONIC BRONCHITIS PATHOGENESIS

•Initiating factor – chronic irritation (tobacco smoke, inorganic dusts. 90% of patients are

smokers)•Bacterial and viral infections are triggers of

acute exacerbation.•The earliest feature of chronic bronchitis is

hypersecretion of mucus.•Accompanying alteration in the small airways

– BRONCHIOLITIS - can result in earlier manifestation of chronic obstruction

•Macro: hyperemia and edema of mucous membranes with excessive mucous or

mucopurulent secretion•Micro:

•Chronic inflammation•Enlargement of mucus-secreting glands of

trachea and bronchi•Increased number of goblet cells•Squamous metaplasia and dysplasia of

bronchial epithelium•Narrowing of bronchioles by mucous

plugging, inflammation and fibrosis up to bronchiolitis obliterans

BRONCHIAL ASTHMABRONCHIAL ASTHMA

Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough.These symptoms are associated with bronchoconstriction and airflow limitation that are at least partially reversible

BRONCHIAL ASTHMA

•ATOPICEvidence of allergic

sensitization in patients with history

of other allergic symptoms

•NON-ATOPICWithout evidence of

allergic sensitization

Bronchospasm can be triggered bydiverse mechanisms: infections, irritants, exercise

ATOPIC ASTHMA

•Classic example of type I IgE-mediated hypersensitivity reaction

•Usually begins in childhood•Triggered by environmental allergens

(dusts, pollens, food etc)•Positive family history of asthma is

common•Positive skin tests

NON-ATOPIC ASTHMA

•No evidence of allergic sensitization•Viral respiratory infections are common

triggers•Hyperirritability of the bronchial tree•Virus –induced inflammation of the

respiratory mucosa lowers the threshold of the subepithelial vagal receptors to

irritants

DRUG-INDUCED ASTHMA

•Aspirin-sensitive asthma occurs in individuals with recurrent rhinitis and

nasal polyps•Sensitivity to small doses of aspirin•Aspirin inhibits the cyclooxygenase

pathway of arachidonic acid metabolism without affecting the lipooxygenase

pathway → ↑ leucotrienes →bronchoconstriction

Morphology

•Mucous plugs with Curschmann spirals and

Charcot-Leyden crystals•Basement membrane thickenning•Inflammation and edema of bronchial

wall•Increase in size of the submucosal

glands•Bronchial smooth muscle hypertrophy

MUCOUS PLUGS

CHARCOT LEYDEN CRYSTALS

CURSCHMANN SPIRAL

BASEMENT MEMBRANE THICKENINGBASEMENT MEMBRANE THICKENINGSMOOTH MUSCLE HYPERTROPHY SMOOTH MUSCLE HYPERTROPHY

HYPRTROPHY OF SUBMUCOSAL GLANDS

BRONCHIECTASISBRONCHIECTASIS

Bronchiectasis is a disease characterized by permanent dilation of bronchi and bronchioles caused by destruction of

the muscle and elastic tissue, resulting from or associated with chronic

necrotizing infections.

Etiology and pathogenesis

•Postinfectious conditions (necrotizing pneumonia)

•Congenital conditions (cystic fibrosis, intralobarsequestartion, ciliary dyskinesia and

Kartagener syndrome, immunodefficiency)

•Bronchial obstruction (tumor, foreign bodies, mucus)

•Others ( Rheumatoid arthritis, SLE, IBD,GVHD)

Morphology

•Bilateral lower lobes involvement•Airways dilatation: cylindrical, fusiform,

saccular•Intense acute and chronic inflammation.

Necrosis. Lung abscess formation

BRONCHECTASIS LOCALIZED

Diffuse interstitial lung diseases

Diffuse Interstitial (Infiltrative, Restrictive) Diseases

•Characterized by reduced expansion of lung parenchyma with decreased

total lung capacity

Diffuse Interstitial (Infiltrative, Restrictive) Diseases

•Heterogeneous group of disorders characterized predominantly by diffuse and usually chronic involvement of the

pulmonary connective tissue, principally the most peripheral and delicate interstitium in the alveolar

walls.

Idiopathic pulmonary fibrosis

Pathogenesis

•“Repeated cycles” of alveolitis•Healing with exuberant fibroblastic

proliferation (mediator TGF-β)

Morphology

•Macro:–Lower lobes

predominance–Cobblestone

pleural surface–Cut surface :

firm, rubbery, white areas (fibrosis) in

subpleural areas and along the

interlobular septa

Microscopically: usual interstitial pneumonia (UIP)

•Patchy interstitial fibrosis•Fibroblastic foci•Honeycomb fibrosis

•Hyperplasia of type II pneumocytes•Mild to moderate inflammation•Smooth muscle hyperplasia•Intimal fibrosis and medial thickening of pulmonary

arteries

Temporal heterogeneity!

Fibroblastic foci

Interstitial fibrosis

Honeycombing

Bronchiolitis obliteransorganizing pneumonia

(BOOP)

Characteristics

•Unknown etiology•Cough and dyspnea•Radiologically: subpleural or peribronchial

patchy areas of airspace consolidation•Spontaneous recovering or treatment with

oral steroids for 6 months

Polypoid plugs of loose connective tissue withinalveolar ducts, alveoli, bronchioles

BOOP

Sarcoidosis

•Systemic disease of unknown cause characterized by noncaseating

granulomas in many tissues•Women>Men•Black>White•Histologic diagnosis by exclusion!•Variable clinical course; 90% of patients

have hilar lymphoadenopathy + lung involvement

Asteroid body Schaumann body

Schaumann body Schaumann body,polarization

Environmentaland occupational

diseases

Hypersensitivity pneumonitis(allergic alveolitis)

•Spectrum of immunologically mediated predominantly interstitial lung disorders

•Abnormal sensitivity to antigen, which involves alveoli ( in contrast to asthma)

•Acute attack (4-6 hours after exposure): fever, dyspnea, cough, leukocytosis

•Chronic disease – progressive respiratory failure.

•Removal of the causative agent prevents transition to fibrosis

Drug- Induced pulmonary diseases

Table 15-7. Examples of Drug-Induced Pulmonary Disease

Bronchospasmβ-Antagonists

BronchospasmAspirin

Hypersensitivity pneumonitis

Nitrofurantoin

Pneumonitis and fibrosisAmiodarone

Hypersensitivity pneumonitis

Methotrexate

Pneumonitis and fibrosisBleomycin

Cytotoxic drugs

Pulmonary DiseaseDrug

Acute lung injury

Acute respiratory distress syndrome (ARDS)

Diffuse alveolar damage (DAD)- morphologic equivalent

Acute respiratory distress syndrome

•Rapid onset of severe life threatened respiratory insufficiency, refractory to

oxygen therapy•Complication of numerous conditions•Radiologically: diffuse alveolar infiltration

Causes of ARDS

•Sepsis*

•Diffuse pulmonary infections*•Gastric aspiration*•Mechanical trauma (including head

injuries)*•Inhaled irritants, smoke, oxygen•Narcotics or barbiturate overdose•Hypersensitivity reactions•Others

Pathogenesis

•Damage to the alveolar capillary membrane ( including microvascular

endothelium and alveolar epithelium) →↑ vascular permeability, alveolar flooding,

loss of diffusion capacity and surfactant abnormality (due to damage to

pneumocytes) → hyaline membranes•Neutrophiles play an important role•Coagulation system dysregulation

Morphology•Acute phase

–Congestion, edema

–Inflammation–Fibrin deposition – Hyaline membranes!

•Organizing phase:–Organization of the fibrin exudate–Thickenning of alveolar septa

–Type II cells hyperplasia

DAD

Macro: heavy, firm, red lung

DAD – Early exudative phase

Hyaline membranes

Type II cells hyperplasia

ORGANIZING PHASE

DAD – Fibroblasticproliferation

Airspace organization

LUNG TUMORS

•Carcinomas – 90-95%•Bronchial carcinoids – 5%•Mesenchymal tumors and

others – 2-5%

Lung cancer incidence

•Most common cause of cancer mortality worldwide

•Occurs between 40 and 70 years, peak in the fifties or sixties.

•2% before age 40•5-year survival rate 16%

Lung cancer etiology and pathogenesis

Tobacco smoking

�average smokers – 10-fold greater risk

� heavy smokers – 60-fold greater risk

�women have a higher susceptibility to carcinogens than men do

� cessation of smoking for 10 years reduces risk but never to control levels

Industrial hazards

•High-dose ionizing radiation•Uranium•Asbestos ( asbestos + smoking = 50-90

times greater risk )

Air pollutions

•Athmosphericpollutants

•Radon

Classification (WHO)•Squamous cell carcinoma•Adenocarcinoma

Acinar, papillary, bronchioloalveolar, solid, mixed

•Large cell carcinoma •Adenosquamous carcinoma •Pleomorphic, sarcomatoid carcinoma•Small cell carcinoma•Large cell neuroendocrine carcinoma •Carcinoid tumor (typical, atypical)•Carcinomas of salivary gland type•Unclassified carcinoma

Clinically important:

•Small cell carcinoma most often metastatic, high initial response

to chemotherapy

•Non- small cell carcinoma less often metastatic, less responsive

Pathology

•75% - area of lung hilus•Small number – on periphery

(adenocarcinoma)•Distant spread occurs by lymphatic and

hematogenous pathwaysadenocarcinoma metastasize at an early stage

SCC metastasize outside the thorax late

Sites of metastases:

•Adrenal – more than half of the cases

•Liver – 30-50%•Brain – 20%•Bones – 20%

Squamous cell carcinoma

•Men > Women•Closely correlated

with smoking history•Most SCC arise

centrally •Squamous

metaplasia and dysplasia are often

seen

Well-differentiated squamouscarcinoma, with keratinization.

Poorly differentiated squamous cell carcinoma

:ImmunophenotypeP63 +High molecular weight keratins +Cytokeratin 7 –TTF1 -

Adenocarcinoma•Most common type of lung

cancer in women and nonsmokers

(still, 75% are found in smokers)

•Smaller than SCC and peripherally located, often

central scar•Grows more slowly than

SCC, but metastasize widely and earlier

:ImmunophenotypeTTF1 +Cytokeratin 7 +Cytokeratin 20 -P 63 -

Bronchioloalveolar carcinoma

•Peripheral portion of the lung as single nodule or in pneumonia-like consolidation

•Histologically – no evidence of stromal, vascular or pleural invasion!

•Growth along preexisting structures without destruction of alveolar architecture

(“lepidic” growth)

BAC, nonmucinous type

•Peripheral lung nodule•No aerogenous spread•Amenable to surgical resection

BAC, nonmucinous type

BAC, mucinous type

•Aerogenous spread solitary nodule

multiple nodules pseudopneumonic consolidation

•Less likely to be cured by surgery

BAC, mucinous type

Small cell carcinoma

•The most aggressive lung tumor

•Occurs both in major bronchi (predominantly) and

on the periphery•Strongly associated with

cigarette smoking

Small cell carcinoma

“Azzopardi phenomenon”

Large cell carcinoma

Undifferentiated carcinoma that lacksthe cytological features of small cell carcinoma

and glandular or squamous differentiation.

On EM – minimal glandular or squamousdifferentiation is common

Large cell neuroendocrine carcinoma has the same molecular changes as small cell

carcinoma

Staging

T1- tumor <3 cm without pleural or main stem bronchus involvement

T2- tumor 3-7 cm or involvement of main stem bronchus 2 cm from carina, visceral pleura or

lobar atelectasisT3- tum. >7cm or with involvement of chest wall,

diaphragm, mediastinal pleura, pericardium, main stem bronchus 2 cm from carina, or entire

lung atelectasisT4- invasion of mediastinum, heart, great vessels,

trachea, esophagus, vertebral body, carina or separate tumor nodules in different ipsilateral

lobe.

Prognosis

•Overall 5-year survival rate is 15%•For localized cases 48% survival rate•Adenocarcinoma and squamous cell ca

tend to remain localized longer and have a slightly better prognosis than

undifferentiated ca.•Small cell ca – resection is ineffective.

Particular sensitivity to radio and chemotherapy. Mean survival ≈ 1 year

Neuroendocrine proliferations and tumors

•Tumorlets•Carcinoids

–typical–atypical

•Small cell carcinoma•Large cell neuroendocrine carcinoma

Tumorlet

•Benign neuroendocrine cell proliferation, resembles carcinoid

•The size is no more than 4 mm•Occur within and around the

bronchovascular sheaths•May occur with or without associated lung

disease

Carcinoid tumorlet

Carcinoid Tumors•Central or peripheral mass•Most are intraluminal

tumor, some infiltrate the lung parenchyma

•Diameter – 3-4 cm

Bronchial carcinoid

Characteristic growth patterns in neuroendocrine tumors.

Typical carcinoid

•Less than 2 mitoses per 10 HPF•No necrosis

Atypical carcinoid

•2-10 mitoses per 10 HPF•Foci of necrosis•More atypia, cellularity, lymphatic invasion

Clinical presentationIntraluminal growth → cough, hemophtysis,secondary infection, bronchiectasis,

emphysema, atelectasis.

Secretory activity → carcinoid syndrome (intermittent attacks of diarrhea, flushing and cyanosis)

Most carcinoids have relatively benign course. (Low grade malignancy).

Can occur in patient with MEN 1.

5-year survival:

•Typical carcinoid - 87%•Atypical carcinoid – 56%•Large cell neurondocrine ca – 27%•Small cell carcinoma – 9%

Other lung tumors•, hemangioma: Mesenchymal

hemangiopericytoma, inflammatory myofibroblastic tumor, leiomyoma,

leiomyosarcoma

•Hodgkin and Hodgkin -: nonHematopieticlymphoma, Langerhans cell histiocytosis

•Hamartoma

Lung hamartoma

•Relatively common lesion•Peripheral solid nodule 3-4 cm, well

circumscribed•Microscopically: nodules of mesenchymal

tissue (cartilage, fat ,fibrous tissue) intersected by epithelial clefts

A hamartoma is a lesion in an organ that is composed of tissue elements normally found at that site, but growing in a haphazardmass

Some features indicate that lung hamartoma is neoplasm, rather than a congenital lesion:

- rarity in childhood-increasing incidence with age-chromosomal aberrations

Metastatic tumors

•Multiple discrete nodules (mostly on periphery)•Solitary nodule

•Endobronchial•Pleural

•“Lepidic” growth, similar to BAC•Growth in peribronchiolar and perivascular

tissue spaces

•Diffuse intralymphatic dissemination

Metastatic carcinoma

Immunohistochemistry helps to find the tumor origin:

cytokeratin 7, TTF1 – lungcytokeratin 20, CDX2 – colon

PSA, PAP – prostatethyroglobulin – thyroid

ER, PR – breast, female genital tract

PLEURAL TUMORS

Malignant pleural tumors

•Primary•Secondary - more common! (most

common origins - lung and breast)

Malignant mesothelioma

•Asbestos exposure related•Long latent period – 25-40 years•Risk for mesothelioma is not

magnified by smoking (in contrast to carcinoma)

Malignant mesothelioma morphology

•Epithelioid type•Sarcomatous type •Mixed

Diffuse spread in the pleura associated withextensive pleural effusion

Malignant mesothelioma.Note the thick, firm, white pleural tumor tissue that ensheathes this bisected lung .

Malignant mesothelioma, epithelial type

Malignant mesothelioma, mixed type

Immunohistochemistry of MM

•Calretinin +•WT 1 +•Thrombomodulin +•Keratin 5/6 +•CEA –•TTF1 –•Different epithelial markers -

Clinical course

•Recurrent pleural effusion•Chest pain, dyspnea•50% die within 12 months•Some improvement with aggressive

therapy (extrapleural pneumonectomy, chemotherapy, radiation)

Solitary fibrous tumor

•Soft tissue tumor, occurs in pleura and other sites

•Often is attached to the pleura by pedicle•Do not produce pleural effusion•Microscopically: whorls of reticulin and

collagen fibers and interspersed spindle cells

•Immunohistochemistry: CD 34+

Solitary fibrous tumor, criteria of malignancy

•Large size (> 10 cm)•Pleomorphism•Necrosis•Mitotic activity (> 4 mitoses for 10 HPF)

Dr. Sofia Zilber